rs7868111

Variant names:

• chr9-134825764-T-C
• rs7868111
• NM_000093.5:c.4955-28T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-134825764-T-C
• chr9-134825764-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000093.5(COL5A1):​c.4955-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,488,796 control chromosomes in the GnomAD database, including 374,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38841 hom., cov: 33)
  • Exomes 𝑓: 0.71 (335731 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.28
• Publications: 8 publications found

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

COL5A1 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome, classic type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
• Ehlers-Danlos syndrome, classic type, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• arterial disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

LOC101448202 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-134825764-T-C is Benign according to our data. Variant chr9-134825764-T-C is described in ClinVar as [Benign]. Clinvar id is 255092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.4955-28T>C		intron_variant	Intron 62 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.4955-28T>C		intron_variant	Intron 62 of 65		NP_001265003.1
LOC101448202	NR_103451.2	n.71-5555A>G		intron_variant	Intron 1 of 1
COL5A1	XM_017014266.3	c.4955-28T>C		intron_variant	Intron 62 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.4955-28T>C		intron_variant	Intron 62 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.4955-28T>C		intron_variant	Intron 62 of 65	2		ENSP00000360885.4
COL5A1	ENST00000460264.5	n.423-28T>C		intron_variant	Intron 3 of 4	3
COL5A1	ENST00000465877.1	n.135-28T>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108617 AN: 152074 Hom.: 38816 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.710

GnomAD2 exomes AF: 0.720 AC: 179176 AN: 248800 AF XY: 0.726

Gnomad AFR exome AF: 0.731

Gnomad AMR exome AF: 0.661

Gnomad ASJ exome AF: 0.780

Gnomad EAS exome AF: 0.778

Gnomad FIN exome AF: 0.721

Gnomad NFE exome AF: 0.703

Gnomad OTH exome AF: 0.712

GnomAD4 exome AF: 0.708 AC: 945974 AN: 1336604 Hom.: 335731 Cov.: 18 AF XY: 0.710 AC XY: 477090 AN XY: 671614

African (AFR) AF: 0.736 AC: 22786 AN: 30954

American (AMR) AF: 0.665 AC: 29368 AN: 44176

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 19783 AN: 25206

East Asian (EAS) AF: 0.732 AC: 28413 AN: 38812

South Asian (SAS) AF: 0.790 AC: 65741 AN: 83266

European-Finnish (FIN) AF: 0.719 AC: 37851 AN: 52676

Middle Eastern (MID) AF: 0.754 AC: 4144 AN: 5498

European-Non Finnish (NFE) AF: 0.698 AC: 697902 AN: 999982

Other (OTH) AF: 0.714 AC: 39986 AN: 56034

GnomAD4 genome AF: 0.714 AC: 108690 AN: 152192 Hom.: 38841 Cov.: 33 AF XY: 0.718 AC XY: 53389 AN XY: 74400

African (AFR) AF: 0.729 AC: 30268 AN: 41520

American (AMR) AF: 0.675 AC: 10322 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2725 AN: 3470

East Asian (EAS) AF: 0.763 AC: 3948 AN: 5174

South Asian (SAS) AF: 0.807 AC: 3895 AN: 4826

European-Finnish (FIN) AF: 0.723 AC: 7655 AN: 10592

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47372 AN: 67994

Other (OTH) AF: 0.709 AC: 1498 AN: 2114

Alfa AF: 0.666 Hom.: 4084

Bravo AF: 0.715

Asia WGS AF: 0.786 AC: 2729 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibromuscular dysplasia, multifocal Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome, classic type, 1 Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.37
DANN	Benign	0.35
PhyloP100		-4.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7868111; hg19: chr9-137717610;